title: Augmented inhibition of tumor cell proliferation in the combined use of disulfiram with ascorbic acid and the involvement of oxygen free radicals.
abstract: To examine the roles of oxygen free radicals in the inhibition of tumor cell proliferation, we have used disulfiram (DS), a metal-chelator, to inactivate superoxide dismutase and ascorbic acid (AsA) to inhibit catalase. Simultaneous addition of DS and AsA to Meth A tumor cells or Ehrlich ascites tumor cells induced marked inhibition of the cell proliferation assessed by [3H]thymidine uptake and trypan blue dye exclusion method. Similar augmented inhibition of Meth A tumor cell proliferation was observed when the cells were pretreated with DS and AsA. However, the addition of catalase (2000 u/ml) nullified the augmentation of anti-proliferative effect which can be induced in the combined use of DS and AsA. These results suggest that the steady-state increase of intracellular oxygen free radicals within tumor cells could be induced in the combined use of DS and AsA.
authors.affiliation: Division of Immunology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mashiba
authors.forename: K
authors.initials: K
authors.lastname: Matsunaga
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004221:Disulfiram / Q000008:administration & dosage / Q000494:pharmacology*; D005609:Free Radicals; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D005609:Free Radicals; D002374:Catalase; D001205:Ascorbic Acid; D010100:Oxygen; D004221:Disulfiram